The entire Research Plan contains proprietary/privileged information that Imbed Biosciences requests not be released to persons outside the Government, except for purposes of review and evaluation. Title: Ultrathin dissolvable antibiofilm wound contact dressing with silver and gallium Summary The health care costs associated with treatment of chronic and burn wounds exceeds $25 billion annually in the U.S. Biofilms are implicated as a key factor responsible for delayed healing in chronic wounds. Many wounds have complex surfaces and debridement can be challenging, leaving biofilm fragments that remain resistant to antimicrobial therapy and act as a nidus for recrudescence of biofilms. This underscores the unmet need for a cost-effective and non-cytotoxic antibiofilm wound dressing. There is currently no commercially available wound dressing that is clinically indicated for dispersal of biofilms in a wound bed. Imbed Biosciences Inc. has developed and commercialized a unique microfilm wound contact dressing with silver nanoparticles, named MicroLyte Ag, based on its patented polymeric multilayer nanofilm technology, that conforms to the micro-contours of a wound bed, provides an intimate and sustained contact of active agents with the wound bed, and requires 100x lower concentration of silver ions (compared to conventional dressings) to achieve therapeutic efficacy without cytotoxicity. MicroLyte Ag is highly effective in killing planktonic bacteria and has demonstrated efficacy in suppression of biofilm formation. However, the next challenge is to create a wound dressing that will stimulate dispersal of established biofilms in wounds. Our preliminary data shows that Ag+ and Ga3+ biofilm, when delivered through polyelectrolyte multilayer nanofilm, achieved 1000x greater reduction in biofilm CFU than a corresponding topical formulation. This research project will test the hypothesis that sensitization of microbes in biofilms by antibiofilm gallium would enable non-cytotoxic levels of antimicrobial silver to kill biofilm-encased bacteria. There is currently no commercial wound dressing or topical formulation that employs gallium as an antibiofilm agent. Our preliminary experiments have shown that MicroLyte Ag-Ga prototypes can achieve up to 4 Log10 CFU reduction in 48 h old P. aeruginosa biofilms and disperse ? 90% of biofilm mass in vitro, despite releasing 5-10x lower levels of Ag+ than commercial antimicrobial dressings that did not exhibit any significant antibiofilm activity. This proposal seeks to advance development of a next-generation antimicrobial-antibiofilm wound dressing containing silver and gallium. The goal of this Phase 1 feasibility research is to: (AIM 1) Identify silver and gallium loadings in MicroLyte Ag-Ga that exert antibiofilm activity against single and multispecies biofilms of P. aeruginosa and S. aureus without in vitro cytotoxicity and, (AIM 2) Evaluate efficacy of MicroLyte Ag-Ga in dispersal of preformed biofilms in splinted murine wounds. For this project, Imbed has assembled a team of researchers with substantial expertise in biomaterials (Agarwal, Dalsin, Pranami, and Abbott), microbiology (Czuprynski), animal wound models (McAnulty) and clinical wound care (McAnulty and Schurr). Successful completion of Phase 1 research will provide feasibility data for a Phase 2 project to study dispersal of biofilms of multiple bacterial strains in murine/porcine wound models.